The pathogenesis of Gaucher's disease is not understood. Previous work in this laboratory has identified the deficiency of glucocerebrosidase and the accumulation of glucocerebroside exclusively in macrophages of the reticuloendothial system. The enzyme has been isolated and purified. Clinical trials of enzyme replacement have been encouraging and are expected to lead to a useful therapeutic application. Further study of the enzyme and the principles governing its incorporation into cells and activity towards stored glucocerbroside are required. A broader understanding of the disease and the mechanisms involved in substrate storage leading to clinical symtoms will be necessary to direct therapeutic strategies. The development of a tissue culture model of the disease using human macrophages will assist in these approaches to elucidating important parameters in the pathogenesis and treatment strategies.